Macrophages play a pivotal role in several immunobiological reactions. This proposal is concerned with those macrophages associated with murine sarcomas and how they may influence the behavior of the tumor. It is proposed to use the cytotoxic drug, cyclophosphamide (CY), as a probing agent, rather than as a therapeutic agent, to induce two distinctive reactions in which macrophages may play an important role. The first is tumor regression, induced by CY injection, and the second is tumor recurrence that follows in nearly all cases after CY-induced regression. The objective is to test three hypotheses that may not be mutually exclusive. (a) That tumor-associated macrophages (TAM) may preferentially eliminate cells damaged by the metabolites of CY and fail to destroy undamaged, tumorigenic cells; (b) that TAM may directly stimulate the proliferation of residual tumorigenic cells or they may enhance their survival by abrogating anti-tumor effector mechanisms, and (c) that newly-arrived tumor-associated monocytes may be responsible for the above effects rather than the more mature, resident TAM. The data obtained will help to elucidate the nature of the effects TAM exert during tumor regression and progression under defined conditions. The long-term objective is to understand the functions of TAM with the ultimate view of controlling tumor growth.